Accurate mass precursor ion data and tandem mass spectrometry identify a class I human leukocyte antigen A*0201-presented peptide originating from vaccinia virus

Kenneth L. Johnson, Inna G. Ovsyannikova, Benjamin J. Madden, Gregory A. Poland, David C. Muddiman

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

We have used accurate mass precursor ion data generated on a hybrid linear-ion trap-Fourier transform ion cyclotron resonance mass spectrometer to augment tandem mass spectrometry (MS/MS) data generated on two different instrument types. Results from these experiments have allowed us for the first time to identify a naturally processed peptide presented by a class I human leukocyte antigen allele (HLA-A*0201) that was isolated from B cells infected by live vaccinia, the viral agent of the smallpox vaccine. The accurate mass data, in conjunction with MS/MS data, was able to identify the sequence IVIEAIHTV (aa 187-195) from the protein thymidylate kinase of vaccinia, distinguishing it from a similar sequence IVLEAIAEH: a "self-peptide" from the human protein phospholipase Cβ3. Accurate mass data for the doubly charged species from the naturally processed and presented peptide was 497.8006, which was within 0.8 ppm of the calculated m/z of 497.8002, while being -37.3 ppm from the calculated m/z (497.7820) of the second-ranked peptide sequence IVLEAIAEH. Accurate mass data ranged from less than 0.1 to 1.2 ppm for other peptides identified in this sample. A BLAST search shows this sequence, IVIEAIHTV, is conserved in the same protein of a number of other orthopoxviruses, including the variola (smallpox) virus. Additionally, accurate mass data were able to uncover a false positive search result that was not distinguished by scoring of the match to the MS/MS data.

Original languageEnglish (US)
Pages (from-to)1812-1817
Number of pages6
JournalJournal of the American Society for Mass Spectrometry
Volume16
Issue number11
DOIs
StatePublished - Nov 2005

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Vaccinia virus
HLA Antigens
Tandem Mass Spectrometry
Viruses
Mass spectrometry
Ions
Peptides
Variola virus
Vaccinia
dTMP kinase
Orthopoxvirus
Smallpox Vaccine
Cyclotrons
Cyclotron resonance
Proteins
Phospholipases
Mass spectrometers
Fourier Analysis
Protein Kinases
Fourier transforms

ASJC Scopus subject areas

  • Structural Biology
  • Spectroscopy

Cite this

Accurate mass precursor ion data and tandem mass spectrometry identify a class I human leukocyte antigen A*0201-presented peptide originating from vaccinia virus. / Johnson, Kenneth L.; Ovsyannikova, Inna G.; Madden, Benjamin J.; Poland, Gregory A.; Muddiman, David C.

In: Journal of the American Society for Mass Spectrometry, Vol. 16, No. 11, 11.2005, p. 1812-1817.

Research output: Contribution to journalArticle

Johnson, Kenneth L. ; Ovsyannikova, Inna G. ; Madden, Benjamin J. ; Poland, Gregory A. ; Muddiman, David C. / Accurate mass precursor ion data and tandem mass spectrometry identify a class I human leukocyte antigen A*0201-presented peptide originating from vaccinia virus. In: Journal of the American Society for Mass Spectrometry. 2005 ; Vol. 16, No. 11. pp. 1812-1817.
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